Baseline vitamin D status is associated with glycemic and weight loss outcomes in patients with type 2 diabetes treated with semaglutide

Objective Semaglutide, a glucagon-like peptide-1 receptor agonist, is an established therapy for type 2 diabetes (T2D), offering robust glycemic control and weight reduction. Vitamin D has been implicated in metabolic regulation, yet its influence on semaglutide-induced outcomes remains unclear. Research design and methods We conducted a retrospective cohort study of 5,384 adults with T2D, enrolled in Leumit Health Services, who initiated semaglutide therapy between February 1, 2019, and December 31, 2022. All patients had documented serum 25-hydroxyvitamin D [25(OH)D] levels prior to treatment initiation. Metabolic outcomes- including glycemic control (HbA1c), body mass index (BMI), and lipid profile- were assessed at 12 months. Associations between baseline 25(OH)D levels and metabolic changes were evaluated using multivariable regression models, adjusted for demographic and clinical covariates. Results The median baseline 25(OH)D level was 19.3 ng/mL. Compared with patients with 25(OH)D levels <15 ng/mL, those with levels of 15–25 ng/mL and >25 ng/mL exhibited greater reductions in HbA1c [ β = −0.083, 95% CI (−0.154 to −0.013), p = 0.020; and β = −0.096, 95% CI (−0.173 to −0.017), p = 0.016, respectively] and BMI [ β = −1.02, 95% CI (−1.46 to −0.58); and β = −1.29, 95% CI (−1.77 to −0.80); both p < 0.0001]. No association was found with lipid profile. Conclusion Higher baseline 25(OH)D levels are independently associated with improved glycemic and weight loss responses to semaglutide in individuals with T2D. Prospective trials are warranted to explore whether vitamin D supplementation may potentiate semaglutide’s metabolic effects.